Allergic asthma is thought to stem from inappropriate immune responses to inhaled antigens. Therefore, to prevent or treat allergic asthma, it is important to identify the cellular and molecular mechanisms that initially give rise to allergic sensitization. Accordingly, our laboratory uses mouse models of asthma to study allergic sensitization through the airway. To do this, we sensitize mice to ovalbumin (OVA) by delivering this protein to the airway together with various adjuvants. Such adjuvants include ligands of toll-like receptors (TLRs), such as lipopolysaccharide (LPS). Pulmonary dendritic cells lining the airway epithelium take up OVA and migrate to draining thoracic lymph nodes to present OVA-derived peptides to nave T cells. We have found that this method of sensitization primes a qualitatively different type of immune response than the more conventional method of sensitization involving intraperitoneal (i.p.) injections of OVA complexed with aluminum hydroxide (alum). Thus, sensitization through the airway, but not through the peritoneum, induces robust T helper (Th)17 responses. These Th17 cells produce IL-17 upon challenge with OVA that in turn leads to airway neutrophilia and airway hyperresponsiveness (AHR). Ongoing Th17 responses to inhaled allergens might therefore distinguish severe asthma from less serious Th2-mediated diseases of the airway. In addition to studying the mechanisms underlying the induction of Th17 cells in the lung, we also study the impact of various environmental pollutants on pulmonary dendritic cell activation, and how these pollutants can act as adjuvants in the lung to promote allergic sensitization through the airway. There are two major subsets of resident lung dendritic cells. One subset displays the cell surface molecule, CD103, whereas the other subset displays a different marker, CD11b. We are comparing the functions of these two dendritic cell subsets following their enrichment by flow cytometry-based sorting and culture with OVA-specific T cells from OT-II mice. The origin of the two major lung resident dendritic cell subsets remains unclear. Although the chemokine receptors, CCR2 and CX3CR1 have both been implicated in the recruitment of monocytes to the lung, it is not known whether monocytes displaying these two molecules give rise to pulmonary dendritic cells having different functional properties. One of the projects in our laboratory is directed at identifying such differences.